Dao Nguyen

Position
Professor, Department of Medicine, McGill University
Director, McGill Antimicrobial Resistance Centre

Research Interests

Pseudomonas aeruginosa; Cystic Fibrosis microbiology and respiratory infections; Antibiotic tolerance and resistance; Antimicrobial discovery; Bacterial biofilms; Host-pathogen interactions; Lung inflammation and innate immunity; Molecular microbiology and bacterial genetics;

Research Orientations

The Nguyen lab is focused on Pseudomonas aeruginosa and chronic airway infections, with a particular focus on cystic fibrosis (CF) lung disease. The lab’s projects range from the molecular microbiology and genetic studies of P. aeruginosa and biofilms, to in-vitro, in vivo and translational studies that probe bacterial-host interactions. Specifically, they are focused on two main themes: 1) Molecular mechanisms of stress responses, oxidative stress and antibiotics tolerance in P. aeruginosa and 2) Bacterial-host interactions in pulmonary innate immunity and inflammation.

1. Stress responses, oxidative stress and antibiotics tolerance in Pseudomonas aeruginosa

Multidrug tolerance severely mitigates the ability of bactericidal antibiotics to kill bacteria, even in genetically drug-susceptible strains. This is a major challenge to the effective treatment of chronic infections such as Pseudomonas aeruginosa (PA) biofilm infections. Using a broad range of approaches, from bacterial genetics, biochemistry and microbiology to in vivo murine models of P. aeruginosa infections, our lab tries to understand the molecular and cellular mechanisms implicated in bacterial stress survival and antibiotic tolerance of P. aeruginosa. We are particularly interested in the stringent response and (p)ppGpp signalling, oxidative stress, biofilm and stationary phase bacterial physiology, and mechanisms of antibiotic lethality. Our goal is to gain mechanistic insights and identify targets or compounds for novel antibacterial discovery.

Selected work:

Nguyen D*, Joshi-Datar A, Lepine F, Bauerle E, Okanami B, Beer K, McKay G, Siehnel R, Schafhauser J, Wang Y, Brittigan B, Singh PK. Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria. Science 2011; 334(6058): 982-6.
Khakimova M, Harrison J, Ahlgren H, English A, Nguyen D*. The stringent response controls catalases in Pseudomonas aeruginosa and is required for hydrogen peroxide and antibiotic tolerance. Bacteriology. May 2013; 195(9):2011-20.
Schafhauser J, Lepine F, McKay G, Ahlgren H, Khakimova M, Nguyen D*. The stringent response modulates 4-hydroxy-2-alkylquinolines biosynthesis and quorum sensing hierarchy in Pseudomonas aeruginosa. Bacteriology. May 2014; 196(9): 1641-50.

2. Bacterial-host interactions in pulmonary innate immunity and inflammation.

Chronic lung disease is the major cause of morbidity in patients with the genetic disease cystic fibrosis (CF), and is characterized by chronic bacterial infections and neutrophilic immunopathology. Our lab is interested in examing host-pathogen interactions to understand the impact of CF lung pathogens on lung inflammation and pathogenicity. We use bacterial genetic approaches, in vitro bacterial-epithelial cell co-culture systems, in vivo murine infection models and translational studies in CF patients to probe host inflammatory and innate immune responses to specific P. aeruginosa strains and mutants. Our goal is to gain insights into novel and clinically relevant host-pathogen interactions implicated in pulmonary immunopathology and to understand how airway bacterial pathogens and P. aruginosa variants contribute to the pathogenesis of chronic CF lung disease.

Selected work:

Lafayette S, Houle D, Radzioch D, Beaudoin T, Hoffman LR, Burns JL, Dandekar A, Smalley N, Chandler J, Zlosnik J, Speert D, Bernier J, Matouk E, Brochiero, Rousseau S, Nguyen D*. Cystic fibrosis-adapted Pseudomonas aeruginosa quorum sensing lasR mutants cause hyper-inflammatory responses. Science Advances July 2015, 1(6), e1500199.
Chekabab S, Silverman R, LaFayette S, Luo Y, Rousseau S, and Nguyen D*. Staphylococcus aureus inhibits Pseudomonas aeruginosa induced IL-8 responses in airway epithelial cells.
Ahlgren HA, Benedetti A, Landry JS, Bernier J, Matouk E, Radzioch D, Lands LC, Rousseau S, Nguyen D*. Clinical outcomes associated with Staphylococcus aureus and Pseudomonas aeruginosa airway infections in adult cystic fibrosis patients. BMC Pulmonary Medicine May 2015, 15 (1):67.
Beaudoin T, Lafayette S, Roussel L, Bérubé J, Desrosiers M, Nguyen D, and Rousseau S. The level of p38α MAPK activation in airway epithelial cells determines the onset of innate immune responses to planktonic and biofilm Pseudomonas aeruginosa. Journal of Infectious Diseases. May 15 2013 207(10): 1544-55.
Nguyen D, Singh PK. Evolving stealth: Genetic adaptation of Pseudomonas aeruginosa during cystic fibrosis infections. Proceedings of the National Academy Science 2006 May 30; 103(22): 8305-6.